Cellular immunity mediated by, among others, cytotoxic T cells (also sometimes referred to as killer T cells or CTLs) or helper T cells, which are antigen-specific T cells, plays a central role in elimination of cancer cells or virus-infected cells from a living body. An antigen-specific T cell recognizes, using its T cell receptor, a bound complex between an MHC molecule (also referred to as an HLA molecule in case of human) on the cell surface of an antigen-presenting cell such as a dendritic cell or macrophage and an antigen peptide which is a fragment peptide of an antigen protein derived from a cancer or virus, and thereby differentiates and proliferates. Antigen peptides presented on the MHC molecules are known to be usually about 8 to 20 amino acids in length. Antigen-specific T cells that thus have differentiated and proliferated exert their anti-tumor or anti-viral effects by specifically injuring cancerous or virus-infected cells that present the complex bound between the antigen peptide and the MHC molecule, or by producing various cytokines.
So-called vaccine therapies in which an antigen protein or an antigen peptide derived from a cancer or virus is administered to potentiate antigen-specific T cells are believed useful for treatment or prevention of cancers and viral infections. Cancerous or viral antigens recognized by T cells have been screened to date for various cancers and virus infections, and many cancer antigen proteins, virus-derived antigen proteins, and antigen peptides derived therefrom have been already identified (Immunogenetics 1995, 41:178; Cancer Immunol. Immunother. 2001, 50:3). For example, one of those antigens, WT1, was originally identified as a causative gene for a childhood renal tumor, that is, Wilms tumor (Nature 1990, 343:774). In normal tissues, the WT1 gene is weakly expressed only in restricted tissues such as kidney, testis, and ovary, whereas it has been shown to be highly expressed in various cancers such as leukemia as well as lung, breast, ovarian, prostatic, bladder, uterine, cervical, gastric, colon, germ cell, hepatic, and skin cancers (JP Kokai H09-104627, JP Kokai H11-35484). Recently, it has been shown that WT1-specific cytotoxic T cells (CTLs) were induced by in vitro stimulation of peripheral blood mononuclear cells from HLA-A2.1- or HLA-A24.2-positive human donors with a 9-mer WT1 peptide comprising an MHC class I binding motif (Immunogenetics 51:99-107, 2000; Blood 95:2198-203, 2000; Blood 95:286-93, 2000). It has also been shown that WT1-specific CTLs were induced by in vivo immunization of mice with a 9-mer WT1 peptide (J Immunol 164:1873-80, 2000; Blood 96:1480-9, 2000) or WT1 cDNA (J Clin Immunol 20:195-202, 2000), and further that the immunized mice reject transplanted tumor cells highly expressing WT1 (J Immunol 164:1873-80, 2000; J Clin Immunol 20:195-202, 2000). These findings demonstrate that WT1 protein is one of cancer antigen proteins, and may provide a measure for cancer vaccines against fluid or solid cancers.
In order to efficiently induce a specific immunity by vaccination, it is effective to administer an antigen protein or an antigen peptide as a principal agent in combination with a non-specific immunopotentiator. Known non-specific immunopotentiators include bacterium-derived components, cytokines, and plant-derived components. In addition, the dosage form of vaccine is also an important factor for efficient induction of specific immunity. For example, aluminium preparations, lipid particles, emulsion preparations, and microspheres are known as dosage forms of vaccines. These substances and dosage forms that effect the enhancement of vaccine efficacies are collectively called adjuvants (Nature Biotech. 1999, 17:1075). At present, the most widely used adjuvant among those as approved for human use is an aluminium preparation, but its ability to induce antigen-specific T cells is low, and side effects such as IgE production have been pointed out as problems.
In the light of the great ability of dendritic cells as antigen-presenting cells to induce antigen-specific T cells, research on cell vaccines has been also conducted in recent years, in which dendritic cells derived from a patient are pulsed in vitro with an antigen protein or an antigen peptide to cause antigen presentation, and then put back into the patient (Nature Med. 1998, 4:328). However, there are many problems to be solved before the cell vaccine therapy can become widely available; it is technically difficult and costly to obtain a large amount of dendritic cells required for the therapy.
Under such circumstances, there has been a need for developing a novel vaccine that enables simple, convenient, and efficient induction of antigen-specific T cells as well as a method of administering the same.